Interleukin-12 is an immunostimulating cytokine that can stimulate both natural killer cells (nk) and t-cells. Because of these properties, IL-12 has been evaluated in animal models for anti tumor activity. These various animal models have shown partial and complete tumor regression, immunity to rechallenge and improved survival following systemic or peritumoral administration of IL-12. Further, IL-2 is also being used for treatment of a proportion of patients with malignancies such as melanoma and renal cell carcinoma, both alone and in combination with other therapeutic agents. However, the use of IL-12 has not gained wider clinical use because of associated problems including rapid plasma clearance, biodistribution to nonrelevant tissues, and high toxicity.
Delivery of IL-12 encapsulated in liposomes has been considered. Additionally, liposomes have been shown to potentiate a broad array of humoral and cellular immune responses. The imunoadjuvant activity of Liposomes has been well studied that it can stimulate antibody responses against liposome associated protein antigens. Due to their molecular properties, antigens can be attached to the external surface, encapsulated within the internal aqueous spaces or reconstituted within the lipid bilayers of the liposomes. Thus, while delivery of IL-12 via liposomes provides attractive advantages, such delivery has not gained wide acceptance clinically. Therefore, there continues to be a need to develop liposomal compositions carrying IL-12 which improve delivery and have reduced minimal toxicity.